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Menthadiene-7-methyl formate
Fragrance raw materials monographs
75S
MENTHADIENE-7-METHYL F O R M A T E Synonyms: Isobergamate; 2-(4-isopropylcyclohexadienyl)ethyl formate; menthadienyl methylethyl)cyclohexadiene-1-ethyl formate. CAS Registry No. 68683-20-5 CAS Registry Name: Cyclohexadiene-l-ethanoi, 4-(1-methylethyl)-, formate Structure:
~
formiate; 4-(1-
OCHO
Description: A colourless to slightly yellow liquid reminiscent of bergamot oil with a woody background. Analytical data on the material as tested by RIFM :
Gas chromatogram Infra-red spectrum Refractive index Specific gravity
on file on file 1.4862 (20°C) 0.991 (25/25°C)
Preparation: Reaction of nopol with formic acid, then reflux and fractionation. Natural occurrence: Has apparently not been reported to occur in nature.
Biological data Acute toxicity. The oral LDs0 in rats was reported as 3.60 ml/kg (3.35-3.85 ml/kg) (Dragoco, 1979) and as > 5 g/kg based on 3/10 deaths at that dose (Moreno, 1977). The dermal LDs0 in rabbits exceeded 5 g/kg based on 0/10 deaths at that dose (Moreno, 1977). Irritation. Application of 0.1 g of 1.5% in petrolatum produced no irritation to the surface of the rabbit eye (Dragoco, 1979). As part of the dermal LDs0 study, 5 g/kg of the undiluted material produced moderate to severe oedema and erythema on rabbits after an occluded application for 24 hr (Moreno, 1977). When 50 human subjects, 39 of whom had some form of eczema, were patched on the shoulder blade with 1.5% in petrolatum for 24 hr, no effects were produced (Dragoco, 1979). A 48-hr closed patch test with 10% in petrolatum on the forearms or backs of 79 volunteers produced no irritation (Epstein, 1977 and 1978; Kligman, 1978), nor did 1% in petrolatum on 50 volunteers (Kligman, 1979) or 1.5% in petrolatum on 25 volunteers (Dragoco, 1979). Sensitization. Three maximization tests (Kligman, 1966; Kligman and Epstein, 1975) were carried out with 10% in petrolatum on 79 volunteers in three separate panels: 1/25 (Epstein, 1977), 4/29 (Epstein, 1978) and 3/25 (Kligman, 1978) sensitization reactions were produced. Three maximization tests (Kligman, 1966; Kligman and Epstein, 1975) were carried out on 75 additional volunteers in three separate panels; no sensitization reactions were produced with 1.5% in petrolatum with one panel (Dragoco, 1979); or with 1% in petrolatum (Kligman, 1979) with the other two panels. The 10% test concentration was based on a reported maximum concentration of 1.0% in consumer products. The International Fragrance Association (IFRA) now restricts the maximum concentration to 0.5% in fragrance compounds (skin concentration). Photosensitization. In a guinea pig photosensitization test, in which the animals were dosed with 1.5% in petrolatum three times a week for 3 wk followed by UV irradiation and then challenged after a 3-wk rest period, 0/20 reactions were observed (Dragoco, 1979).
Status I F R A (1986) has published a guideline recommending that it should not he used at a level over 0.5% in fragrance compounds.
References Dragoco, Inc. (1979) Private communication to RIFM, I March, 23 April, 1 & 8 May, and 1 June. Epstein W. L. (1977) Report to RIFM, 1 July. Epstein W. L. (1978) Report to RIFM, 28 April. IFRA (1986) Code of Practice, February. International Fragrance Association, Geneva. Kligman A. M. (1966) The identification of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact sensitizers. Journal of Investigative Dermatology 47, 393--409.
76S
R.A. Fogo et al.
Kligman A. M. (1978) Report to RIFM, 26 October. Kligman A. M. (1979) Report to RIFM, 11 September and 7 December. Kligman A. M. and Epstein W. (1975) Updating the maximization test for identifying contact allergens. Contact Dermatitis 1, 231-239. Moreno O. M. (1977) Report to RIFM, 22 August.
75S
MENTHADIENE-7-METHYL F O R M A T E Synonyms: Isobergamate; 2-(4-isopropylcyclohexadienyl)ethyl formate; menthadienyl methylethyl)cyclohexadiene-1-ethyl formate. CAS Registry No. 68683-20-5 CAS Registry Name: Cyclohexadiene-l-ethanoi, 4-(1-methylethyl)-, formate Structure:
~
formiate; 4-(1-
OCHO
Description: A colourless to slightly yellow liquid reminiscent of bergamot oil with a woody background. Analytical data on the material as tested by RIFM :
Gas chromatogram Infra-red spectrum Refractive index Specific gravity
on file on file 1.4862 (20°C) 0.991 (25/25°C)
Preparation: Reaction of nopol with formic acid, then reflux and fractionation. Natural occurrence: Has apparently not been reported to occur in nature.
Biological data Acute toxicity. The oral LDs0 in rats was reported as 3.60 ml/kg (3.35-3.85 ml/kg) (Dragoco, 1979) and as > 5 g/kg based on 3/10 deaths at that dose (Moreno, 1977). The dermal LDs0 in rabbits exceeded 5 g/kg based on 0/10 deaths at that dose (Moreno, 1977). Irritation. Application of 0.1 g of 1.5% in petrolatum produced no irritation to the surface of the rabbit eye (Dragoco, 1979). As part of the dermal LDs0 study, 5 g/kg of the undiluted material produced moderate to severe oedema and erythema on rabbits after an occluded application for 24 hr (Moreno, 1977). When 50 human subjects, 39 of whom had some form of eczema, were patched on the shoulder blade with 1.5% in petrolatum for 24 hr, no effects were produced (Dragoco, 1979). A 48-hr closed patch test with 10% in petrolatum on the forearms or backs of 79 volunteers produced no irritation (Epstein, 1977 and 1978; Kligman, 1978), nor did 1% in petrolatum on 50 volunteers (Kligman, 1979) or 1.5% in petrolatum on 25 volunteers (Dragoco, 1979). Sensitization. Three maximization tests (Kligman, 1966; Kligman and Epstein, 1975) were carried out with 10% in petrolatum on 79 volunteers in three separate panels: 1/25 (Epstein, 1977), 4/29 (Epstein, 1978) and 3/25 (Kligman, 1978) sensitization reactions were produced. Three maximization tests (Kligman, 1966; Kligman and Epstein, 1975) were carried out on 75 additional volunteers in three separate panels; no sensitization reactions were produced with 1.5% in petrolatum with one panel (Dragoco, 1979); or with 1% in petrolatum (Kligman, 1979) with the other two panels. The 10% test concentration was based on a reported maximum concentration of 1.0% in consumer products. The International Fragrance Association (IFRA) now restricts the maximum concentration to 0.5% in fragrance compounds (skin concentration). Photosensitization. In a guinea pig photosensitization test, in which the animals were dosed with 1.5% in petrolatum three times a week for 3 wk followed by UV irradiation and then challenged after a 3-wk rest period, 0/20 reactions were observed (Dragoco, 1979).
Status I F R A (1986) has published a guideline recommending that it should not he used at a level over 0.5% in fragrance compounds.
References Dragoco, Inc. (1979) Private communication to RIFM, I March, 23 April, 1 & 8 May, and 1 June. Epstein W. L. (1977) Report to RIFM, 1 July. Epstein W. L. (1978) Report to RIFM, 28 April. IFRA (1986) Code of Practice, February. International Fragrance Association, Geneva. Kligman A. M. (1966) The identification of contact allergens by human assay. III. The maximization test. A procedure for screening and rating contact sensitizers. Journal of Investigative Dermatology 47, 393--409.
76S
R.A. Fogo et al.
Kligman A. M. (1978) Report to RIFM, 26 October. Kligman A. M. (1979) Report to RIFM, 11 September and 7 December. Kligman A. M. and Epstein W. (1975) Updating the maximization test for identifying contact allergens. Contact Dermatitis 1, 231-239. Moreno O. M. (1977) Report to RIFM, 22 August.